Calmodulin is an extremely important protein. We must know its structure in order to understand the conformational changes associated with calcium binding and its interactions with fifteen or more calmodulin binding proteins. We can routinely grow small crystals (less than 0.01mm) of calmodulin. However, it takes six months to grow crystals large enough (0.25mm) for X-ray diffraction data collection. We will continue our intensive efforts to determine what aspects of calmodulin purification and crystallization are critical for the growth of large crystals. We will complete the ongoing work of recording and processing a 5 Angstrom set of data from the few 0.2 mm crystals available. We will perform "self-rotation" Patterson superposition calculations to determine the spatial relationship of isologous domains within calmodulin. "Cross-rotation" calculations against the known "EF-hand domain" structure from parvalbium can confirm the existence of and locate homologous domains in calmodulin. We have processed a set of 5 Angstrom data from S-100b, which contains an EF-hand domain. We are now performing rotation function calculations. By fall, 1980, we should be able to record data on our multiwire area diffractimeter (being developed as a "national resource" RR01135). Our crystals of S-100 and of crayfish sarcoplasmic calcium binding protein diffract to 2.5 A resolution. With both we have formed Gd3 ion substituted isomorphous heavy atom derivations. We should solve both structures to atomic resolution within eighteen months.